Testing for Proteins with Polyglutamine Expansions in the Stanley Foundation Brain Collection




Alan H. Sharp*, Chuanyi

Zhang, Scott Maas, Jesse Mez and Christopher a. Ross

Johns Hopkins University, Department of Psychiatry and Behavioral

Sciences, Baltimore, MD.

Susceptibilities to schizophrenia and

bipolar disorder are thought to be inherited and these diseases

share certain features with inherited progressive

neurodegenerative diseases known to be caused by expansions of

polyglutamine tracts in proteins. For example, there is evidence

of anticipation in schizophrenia and bipolar disorder as in known

polyglutamine-expansion diseases. In schizophrenia, there is

evidence of overall atrophy of the brain and in some cases of a

progressive course. Therefore, we are screening the Stanley Brain

Collection and tissue from other sources for proteins with

polyglutamine expansions to determine whether such proteins may

contribute to susceptibility to schizophrenia and bipolar

disorder. We are using two approaches to screen for polyglutamine

expansions. First, expansions can be detected on Western blots of

brain tissue using the monoclonal antibody 1C2. This antibody

selectively recognizes tracts of about 20 or more glutamines, a

threshold which corresponds well with the threshold for disease

in most of the polyglutamine diseases. A second approach is to

detect, by immunohistochemistry, intranuclear inclusions which

are now considered a hallmark of polyglutamine expansion

diseases. Intranuclear inclusions can be detected with the

anti-polyglutamine antibody 1C2 or with anti-ubiquitin

antibodies. This work will test the hypothesis that proteins with

polyglutamine expansions may contribute to susceptibility to

schizophrenia and bipolar disorder.